Our research aims at uncovering key mechanisms and principles that govern the distribution and trafficking of major lipid species in human cells.
We focus on lipids that are stored in excessive amounts in human lipid storage diseases: cholesterol and sphingolipids accumulate in several inherited lysosomal storage diseases, lipid droplet cholesteryl esters are the storage form of excess cholesterol in atherosclerosis and triglycerides are the storage form of excess energy in obesity. The regulated metabolism and exchange of lipids between these storage organelles, membrane bilayers and the extracellular environment is of key importance for several physiological functions of cells. In turn, their disturbances are associated with the most common diseases globally, including cardiovascular disease, metabolic syndrome and fatty liver.
Image: A Transmission electron microscopy image of a human epithelial A431 cell harbouring multiple lipid droplets, which display numerous contacts with the ER and mitochondria.
Analyzing lipids is not trivial. We employ novel techniques to visualize lipids in living cells and tissues, and develop assays to quantitatively analyze lipid trafficking and metabolism. Besides unraveling basic lipid transport mechanisms, these methods are employed to monitor subtle changes in lipid handling mechanisms at the cellular level between individuals. In the long run, these methods will assist in personalized assessment, monitoring and prevention of lipid related pathological conditions in man.
Image: Human A431 epithelial cells were incubated with fatty acid for 1 hour and imaged live with 3D-SIM microscopy. Green corresponds to eGFP-tagged endoplasmic reticulum membrane protein implicated in lipid metabolism. Magenta shows lipid droplets and mitochondria, labelled by a lipophilic dye.
Lipid distribution and exchange in cells is dictated both by active, protein-driven processes and by biophysical interactions between lipids and proteins. In this context, our research is part of the Centre of Excellence in Biomembrane Research, ProLipids. ProLipids focuses on clarifying the dynamics of lipid-protein interactions and their functional implications. We bridge biochemical and cell biological experiments to theory and computer simulations to generate added value. This enables precise determination of the mechanisms and physicochemical processes modulating functions in cell membranes. We aim to train experts with a deep and broad multi-disciplinary view on this developing area.
Image: Visualization of lipid droplets in a U2OS osteosarcoma cell overexpressing low-density lipoprotein receptor (LDLR). Lipid droplets are shown in green, cell nucleus in blue and the cytoplasm in red (only intense areas).